Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II trial

Abstract

Objective. To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA).Methods. In this 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) >2 cm who had previously taken disease-modifying antirheumatic drugs (DMARDs), including anti-tumor necrosis factor (anti-TNF) agents, were randomized (1:1: 1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score.Results. Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P ‫؍‬ 0.006) and 30/10 mg/kg (P ‫؍‬ 0.022) groups, but not for 3 mg/kg group (P ‫؍‬ 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF-36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms.Conclusion. The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by both arthritis and psoriasis ClinicalTrials.gov identifier: NCT00534313.

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 + T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

“…On one hand, T-cell activation facilitated by B7 costimulation has become widely exploited with B7-neutralizing therapies in a variety of human autoimmune disorders (2)(3)(4)(5)(6). On the other hand, B7 costimulation also maintains Tregs at expanded levels that averts multiorgan systemic autoimmunity (9,10).…”

“…Reciprocally, soluble recombinant formulations of the natural high-affinity B7 ligandcytotoxic T-lymphocyte antigen 4 fused with human Ig (CTLA4-Ig), which blocks B7 costimulation-are efficacious in neutralizing aberrant T-cell activation in autoimmune disorders such as rheumatoid arthritis and juvenile idiopathic arthritis (2). Ongoing studies suggest that these therapeutic benefits also extend to many other types of autoimmunity including psoriasis, systemic lupus erthematosus, multiple sclerosis, and type 1 diabetes (3)(4)(5)(6). Interestingly, however, the protective benefits of B7 blockade are not universal as CTLA4-Ig is distinctively nonefficacious for inflammatory bowel disease (7) and can induce intestinal inflammation among individuals with unrelated autoimmune disorders (8).…”

Combination Biologic Treatment of Refractory Psoriasis and Psoriatic Arthritis

“…However, eventually psoriatic skin and joint involvement became refractory to this combination biologic therapy, and ustekinumab was tried. This combination therapy has not been used in PsA, but recent reports indicate that abatacept, although effective in patients with PsA when compared to placebo, has lower response rates than those seen with anti-TNF inhibitor therapy 22,23 .…”

Biotech on the Rise: The Treatment of Psoriasis with Biological Drugs

“…Abatacept is currently approved for the treatment of rheumatoid arthritis (Bristol-Myers Squibb, 2009). A phase II study has been terminated for psoriatic arthritis and it showed that 10 mg/kg may be an effective treatment (Mease et al, 2011).…”